Acquired immune deficiency syndrome (hereinafter "AIDS") is defined as a disease in an individual less than 60 years of age characteristic of a defect in cell-mediated immunity which arises in a person without known predisposition for diminished resistance (see Morbidity and Mortality Weekly Report 31:507 (1982)). The common denominator of patients with AIDS is a profound but selective abnormality of immunoregulation manifest by susceptibility to opportunistic infections and malignancies (e.g., Kaposi's sarcoma) characteristic of certain genetic and iatrogenic immune deficiencies (see Fauci, A. S., Ann. Intern. Med. 100:92 (1984) and Gottlieb, M. S., Ann. Intern. Med. 99:208 (1983)). Virtually all individuals having AIDS show a deficiency in cellular immune responses (see Masur, H. M., Michelis, M. A., Greene, J. R., Onorato, I., Vande Stouwe, R. A., Holzman, R. S., Wormser, G., Brettman, L., Lange, M., Murray, H. W., and Cunningham-Rundles, S., N. Engl. J. Med. 305:1431 (1981) and Gottlieb, M. S., Schroff, R., Schanker, H. M., Weisman, J. D., Fan, P. T., Wolf, R. A., and Saxon, A., N. Engl. J. Med. 305:1426 (1981)).
Most patients with AIDS give a history of nonspecific complaints lasting from two to eight months or more. Dr. Thomas Quinn of the National Institute of Allergy and Infectious Diseases has suggested that the term "AIDS-related complex" (hereinafter "ARC") be used to describe such individuals with prodromal or "pre-AIDS". A diagnosis of ARC is based upon the occurrence of a combination of clinical findings and laboratory abnormalities, listed below and fully described in Krause, R. M., Rev. Infect. Dis. 6:270 (1984).
______________________________________ Diagnosis of ARC ______________________________________ Two clinical findings plus Two laboratory abnormalities Fever &gt; 3 months .dwnarw.T-helper cells Weight loss &gt; 10 percent .dwnarw.T-helper/T-suppressor ratio BWT* Lymphadenopathy, 3 months .uparw.Serum globulins Diarrhea .dwnarw.Blastogenesis Fatigue Anergy Night sweats ______________________________________ *BWT = body weight total.
It has been demonstrated that supernatants from lectin-free cultures of peripheral blood mononuclear cells (hereinafter "PBMC") obtained from certain homosexual males with AIDS or ARC contain soluble suppressor factors (hereinafter "SSF") which inhibit (i) spontaneous and pokeweed mitogen-derived B cell differentiation into plasmacytes, and (ii) T cell blastogenic responses to antigen (see Laurence, J., Gottlieb, A. B. and Kunkel, H. G., J. Clin. Invest. 72:2071 (1983)). These SSF are the product of the interaction of T cells with adherent normal cells. An adherent cell as used herein is a mononuclear cell identified as a monocyte (a) by its capacity to bond to a plastic surface; (b) by not possessing B or T-cell surface markers, i.e., surface immunoglobulin and E-rosetting capacity; and (c) by its ability to be tagged by antibody 63D3 which is a monoclonal antibody against human monocytes (Becton-Dickenson, California). That is, T cells or T cell derived factors from ARC or AIDS patients (hereinafter collectively "AIDS patients"), but not from healthy homosexual or heterosexual controls, or heterosexual individuals with Epstein-Barr virus or cytomegalovirus mononucleosis, can interact with adherent normal cells in the formation of SSF (see Laurence, J., Gottlieb, A. B. and Kunkel, H. G., J. Clin. Invest. 72:2071 (1983)).
Human T cell hybridomas secreting molecules able to interfere with T cell-directed polyclonal immunoglobulin synthesis independent of T cell mitogenesis (see Grillot-Courvalin, C., Dellagi, K., Chevalier, A. and Brouet, J. C., J. Immunol. 129:1008 (1982) and Grillot-Courvalin, C. and Brouet, J. C. Nature 292:844 (1982)), or with antibody production directly at the level of the B cell (see Greene, W. C., Fleisher, T. A., Nelson and D. L., Waldmann, T. A., J. Immunol. 129:1986 (1982), have been described. These studies utilized PBMC from healthy individuals enriched for activated suppressor T cells by in vitro exposure to concanavalin A (see Greene, W. C., Fleisher, T. A., Nelson, D. L. and Waldmann, T. A., J. Immunol. 129:1986 (1982)), or unstimulated T cells from patients with common variable hypogammaglobulinemia (see Grillot-Courvalin, C., Dellagi, K., Chevalier, A. and Brouet, J. C., J. Immunol. 129:1008 (1982) and Grillot-Courvalin, C. and Brouet, J. C., Nature 292:844 (1982) and Depper, J. M., Leonard, W. J., Black, R. M., Waldmann, T. A. and Greene, W. C., Clin. Res. 30:346A (1982)). These T cell hybridomas only secrete non-specific suppressor factors, i.e., the suppressor factors do not specifically inhibit T cell-dependent immune responses. Further, there is no evidence that these non-specific suppressor factors have in vivo efficacy as immunosuppressive agents. In addition, all of the above-described hybridomas are constitutive producers of suppressor factors, i.e., the production of these suppressor factors by the hybridomas is not controllable.
Soluble immune response suppressor factors from several murine T cell hybridomas have been recovered and thus demonstrate that a continuous microphage cell line can be employed to process or generate soluble immune reponse suppressor factors under the direction of T lymphokines (see Aune, T. W. and Pierce, C. W., Proc. Nat'l Acad. Sci. 78:5099 (1981)).
At least two soluble immune response suppressor factors have been identified in man (see Fleisher, T. A., Greene, W. C., Blaese, R. M. and Waldmann, T. A., J. Immunol. 126:1192 (1981)) and Greene, W. C., Fleisher, T. A. and Waldmann, T. A., J. Immunol. 126:1185 (1981)), one of which has been produced by a continuous T cell line (Greene, W. C., Fleisher T. A. and Waldmann, T. A., J. Immunol. 126:1185 (1981)). SSF from AIDS patients, as well as SSF from the T cell hybridomas of the present invention, are distinguishable from the above-described factors by the restriction of activity to T cell-dependent processes, and the lack of susceptibility to effects thereon of specific sugars. The activity of the known suppressor factors described above can be specifically inhibited by high concentrations, i.e., greater than 50 mM, of sugars such as L-rhamnose, .alpha.-methylmannoside, L-fucose, and N-acetyl-D-glucosamine.